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On Darwin, 



Snow, and 



Deadly 



Diseases 



An evolutionary approach to 



disease control could vastly 



improve public health 



by Paul W. Ewald 



The other passengers on the London 

 train must have dismissed me as another 

 mental casualty of twentieth-century 

 urban life. I had looked out of the train 

 window, let out a "Ha!" and then chuck- 

 led, nodding my head as though I had just 

 been told a joke by an invisible friend. But 

 I didn't care. I had just made a connection 

 between discipUnes that was symboUzed 

 by what I saw through the window. 



The day began like most that summer of 

 1984. I entered the Ubrary of the London 

 School of Hygiene at opening time, hold- 

 ing a plastic shopping bag filled with 

 about a thousand note-covered index 

 cards. Surviving a probing glance from the 

 front desk, I scaled a flight of stairs and 

 hustled to a secluded table sandwiched be- 

 tween floor-to-ceiling shelves of old med- 

 ical journals. I removed half of my cards 

 and a thermos of coffee tiiat I had hidden 

 in the bag, leaving a hand-width passage- 

 way to a cache of cookies, which would 

 fuel me until the library closed. I con- 

 cealed the cup with the bag and stowed the 

 thermos below the table, out of the Ubrar- 

 ian's Une of sight, to avoid the wrath I in- 

 curred when my operations were less clan- 

 destine. I then set to work. 



I was trying to find out why some dis- 

 eases are so dangerous and others merely 

 annoyances. My interest had been sparked 

 several years earlier when I read Man 

 Adapting, by bacteriologist Rene Dubos. I 

 was surprised by his statement, "Given 

 enough time a state of peaceful coexis- 

 tence eventually becomes estabhshed be- 

 tween any host and parasite." 



I saw no reason why natural selection 

 would always lead to peaceful coexis- 

 tence, although it might do so in certain 

 circumstances. Consider a population of 



42 Natural History 6/94 



viruses living within a human host. What 

 if one variant in this population is more 

 adept at exploiting the host's body? Repli- 

 cating more rapidly, it would win the evo- 

 lutionary race with its viral competitors 

 and become the predominant variant in the 

 population. It would also make the host 

 sicker and more contagious. 



But if the long-term survival of such a 

 virus depends upon its being transmitted 

 directly from host to host, as is the case 

 with the virus that causes the common 

 cold, then the rapid reproducer may pay a 

 high price for its virulence. If the illness is 

 severe enough to immobilize the host, 

 contact with new hosts will be drastically 

 reduced. A more slowly reproducing, 

 milder virus — perpetually being trans- 

 ported by a mobile host to new contacts — 

 would be more likely to prosper. 



If host-pathogen relations always fol- 

 lowed this scenario, Dubos's generaliza- 

 tion would be reasonable; viruses would 

 evolve toward a relatively mild state of co- 

 existence with their hosts. 



But, I reasoned, what if the pathogen 

 could be transmitted even when the host 

 was immobilized? Then the more rapidly 

 rephcating, abusive organism might get 

 the competitive advantages of high repro- 

 duction at a bargain price. This seemed to 

 be the case with Plasmodium falciparum, 

 a pathogen that causes malaria. Even 

 when its host is immobilized, this proto- 

 zoan is still easily transmitted to other 

 people by mosquitoes. Generalizing from 

 this argument, I predicted that disease or- 

 ganisms transmitted by biting arthropod 

 vectors should be more severe than those 

 transmitted directly from person to person. 

 I searched the epidemiological Uterature 

 and found that the prediction passed the 

 test. Vector-borne pathogens like P. falci- 

 parum and the yellow fever virus are sig- 

 nificantly more severe than such host- 

 borne viruses as the common cold. 



Evolution may involve long spans of 

 time, but it can be rapid if generations are 

 short and the culling of competitors is in- 

 tense. Use of antibiotics, for example, can 

 cause staphylococcus bacteria in hospitals 

 to evolve high levels of resistance within a 



few weeks. If our technology can acceler- 

 ate the evolution of a bacterium, couldn't 

 other human activities also cause 

 pathogens to evolve rapidly? My attention 

 was drawn to diarrhea. 



Each year millions of people die from 

 diarrheal diseases, but the organisms that 

 cause diarrhea are not equally culpable. 

 Some cause deadly diseases hke cholera, 

 typhoid fever, and dysentery, but others 

 rarely kill. Are the classic killers mal- 

 adapted organisms that will eventually 

 evolve toward peaceful coexistence, or are 

 they severe because our activities have 

 made them severe? 



This was the question that brought me 

 to the London School of Hygiene. On that 

 summer day, punctuated by surreptitious 



An 1858 Punch cartoon depicted 

 pollution on the Thames. The skeleton is 

 facing the residential area where John 

 Snow completed his classic study of 

 cholera-laden water supplies. 



The Granger Collection 



